Among the vertebrates, the ability of lizards to autotomize or self-amputate and then regenerate a new tail is one of the most striking examples of musculoskeletal tissue repair. Lizards display two remarkable features among vertebrates in their musculoskeletal regenerative processes: 1) the ability to regenerate hyaline cartilage skeleton and 2) the ability to regenerate functional muscle groups with the appropriate shape and tendinous connections. The regenerative process has not been studied by molecular analysis due to lack of genomic reagents. Recently, draft genome sequence of the green anole lizard, Anolis carolinensis, has been released with EST and cDNA sequencing expected. This presents a unique opportunity to elucidate the genetic regulation of tail musculoskeletal regeneration and to generate biological and bioinformatic resources for future work in the Anolis model. We hypothesize that genes identified in patterning and differentiation of mesenchymal stem cells and satellite cells of the musculoskeletal system in other vertebrates will play a key role in regulating Anolis tail regeneration. We will develop molecular reagents for examining gene expression levels and cellular distribution of expression during musculoskeletal regeneration. Furthermore, we will isolate satellite cells as the first cell culture model for Anolis, which would provide a key biological resource for future functional studies. Identification of regenerative mechanisms used by Anolis and application of these studies to mammalian systems would have a profound impact on the development of future regenerative medical therapies. PUBLIC HEALTH RELEVANCE: Lizards display the remarkable ability to regenerate their tails after self-amputation, forming new muscle groups and hyaline cartilage, which is a tissue that are currently difficult to medically regenerate. The genome of the green anole lizard, Anolis carolinensis, has been sequenced, giving us a unique opportunity to examine the molecular control of musculoskeletal regeneration. These findings will help development of innovative therapies for regeneration and repair of cartilage and muscle.